Negative regulation of interleukin 1β expression in response to DnaK from Pseudomonas aeruginosa via the PI3K/PDK1/FoxO1 pathways |
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| Institution: | 1. Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Republic of Korea;2. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, Nankai University, Tianjin 300071, China;1. College of Veterinary Medicine, Midwestern University, Glendale, AZ, United States;2. Department of Animal Care and Technologies, Arizona State University, United States;3. Department of Microbiology and Immunology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, United States;4. Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, United States;5. Department of Biomedical Sciences, Idaho College of Osteopathic Medicine, United States;1. Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran;2. Iranshahr University Medical Sciences, Iranshahr, Iran;3. Department of Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Parasitology and Mycology, Shahid Beheshti University of Medical Sciences, Tehran, Iran;1. Department of Animal Biology, Biology Institute, State Campinas University, Campinas, São Paulo, Brazil;2. Department of Genetics and Evolution, Microbiology and Immunology, Biology Institute, State Campinas University, Campinas, São Paulo, Brazil;3. Superintendência de Controle de Endemias, Seção Técnica de Pesquisa, Controle deVetores, Campinas, São Paulo, Brazil;4. Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, São Paulo, Brazil;1. Department of Animal Medicine, Infectious Diseases, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Sharkia 44511, Egypt;2. Veterinary Diagnostic Laboratory and Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA;3. Department of Microbiology, Faculty of Pharmacy, Zagazig University, Zagazig, Sharkia 44519, Egypt;1. Bacteriology, Immunology and Mycology Department, Faculty of Veterinary Medicine, Suez Canal University, Egypt;2. Animal Health Research Institute, Dokki, Giza, Egypt;3. Microbiology and Immunology Department, Faculty of Pharmacy, Suez Canal University, Egypt;1. College of Animal Science, Tarim University, Alar, Xinjiang 843300, China;2. Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China |
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| Abstract: | Interleukin (IL)-1β is crucial for a wide range of inflammatory responses. Previously, we reported that IL-1β is produced in response to Pseudomonas aeruginosa-derived DnaK via NF-κB and JNK pathways; however, the signaling pathways that counter the process to maintain IL-1β homeostasis are unknown. Here, we show that DnaK-mediated expression of IL1β is increased markedly in macrophages upon blockade of PI3K/PDK1. This was verified by measuring released IL-1β protein. The negative effect of PI3K on IL-1β production was dependent on suppression of both NF-κB and JNK activation. Intriguingly, PDK1 (an underlying mediator of PI3K) acted as an upstream regulator for the activation of NF-κB, but downregulated JNK activation. Furthermore, production of IL-1β and activation of JNK were triggered by inhibition of phosphorylated FoxO1; phosphorylation of FoxO1 was controlled by PDK1 signaling in response to DnaK. Thus, IL-1β production is modulated by P. aeruginosa-derived DnaK via cross-talk between JNK and PI3K/PDK1/FoxO1 pathways. |
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| Keywords: | DnaK FoxO1 IL-1β PDK1 PI3K |
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